operational vector-borne disease surveillance and ...

Operational Vector-borne Disease Surveillance and Control: Closing the Capabilities Gap through Research at Overseas Military Laboratories

186720

MAJ Brian P. Evans, MS, USA CPT Jeffrey W. Clark, MS, USA LT Kathryn A. Barbara, MSC, USN LT Kirk D. Mundal, MSC, USN LT Barry D. Furman, MSC, USN James C. McAvin MAJ Jason H. Richardson, MS, USA ABSTRACT

Malaria, dengue fever, chikungunya virus, leishmaniasis, and a myriad of other vector-borne diseases pose significant threats to the warfighter and to the overall combat effectiveness of units. Military preventive medicine (PM) assets must accurately evaluate the vector-borne disease thre'!t and then implement and/or advise the commander on countermeasures to reduce a particular threat. The success of these measures is contingent upon the biology of the disease vector and on the tools or methods used to conduct vector/pathogen surveillance and vector control. There is a significant gap between the tools available and those required for operational PM assets to provide real-time, effective surveillance and control. A network of US Army and US Navy overseas laboratories is focused on closing the current capabilities gap. Their mission is to develop and field test tools and methods to enhance the combatant commander's ability to identify and mitigate the threat posed by these vector-borne diseases. INTRODUCTION

Since its inception, the US military has consistently been called upon to wage battles and to conduct peacekeeping and humanitarian relief operations in locations of the world where the most formidable enemy is often a tiny, 6- or 8-legged creature. Indeed, in every war fought by the United States up through the Vietnam conflict, the number of casualties caused by arthropod-borne diseases has significantly exceeded the number of battlefield casualties.' It was the pioneering efforts of Walter Reed, William Gorgas, and others that helped to decipher the link between microbes, human disease, and mosquito vectors? Their discoveries led the way in the fight against typhoid fever, yellow fever, malaria, and other diseases that had plagued military and civilian populations for millennia.

17,000 troops acquired malaria. lOver 24,000,000 person days were lost during World War II to malaria and other arthropod-borne diseases such as scrub typhus and dengue feveL l In 1943, Allied forces averaged 208 new cases of malaria per 1,000 Soldiers stationed in the south Pacific. 3 In the Vietnam conflict, annual case rates of malaria reached as high as 600 per 1,000 troops.' In the I940s, entomologists from the US Department of Agriculture developed methods and equipment to use DDT* to control mosquitoes, lice, and other vectors. In collaboration with military entomologists, they developed insecticide dispersal equipment and implemented malaria eradication programs which together reduced the number of malaria cases in the south Pacific to 5 per 1000 Soldiers by 1945. 3

In spite of these discoveries, malaria continued to take

Despite these early successes, there has been a dramatic resurgence of mosquito-borne diseases _

its toll on US forces. During World War I, almost

*Dichlorodiphenyltrich loroethane

16

http://www.cs.amedd.army.mil/dasqaDocuments.aspx?type= 1

during the post-DDT era, and today's military continues to face a significant threat from arthropod vectors. While significant strides have been made in the implementation of personal protective measures, including malaria chemoprophylaxis, bed nets, repellents, and permethrin-treated uniforms, the battle against arthropod-borne disease is far from won. Compliance with such measures remains a problem, as evidenced from a survey of Soldiers returning from Afghanistan. 4 In general, though, the advances in science and medicine have been outpaced by the adaptability of vectors and the evolution of pathogens. Novel more efficient strategies to reduce transmission of vector-home diseases are required if the military is to effectively combat this threat. The required tools would allow deployed PM personnel to accurately evaluate the risk of disease transmission through vector/pathogen surveillance, and subsequently implement control measures to break the cycle of transmission. However, there currently exists a gap between what preventive medicine assets have at their disposal for surveillance and control and what they require to more effectively minirllize the potential for arthropod-borne disease transrllission. Effective control measures are only achievable through the use of real-time, accurate surveillance tools along with a sufficient understanding of the biology and behavior of problem vectors. US Army, Navy, and Air Force entomologists stationed in 5 overseas laboratories are focused on developing and evaluating tools and methods that would fill this capabilities gap: • Thailand-the Armed Forces Research Institute of Medical Sciences (AFRIMS)

borne disease threats (malaria, dengue fever, chikungunya virus, visceral leishmaruasis, and cutaneous leishmarnasis).5 DISEASE OVERVIEW

Malaria

Annually, 300 to 500 rrullion people are infected with malaria, with 1.5 to 2.7 million fatalities (mostly children). 6 Several hundred cases of malaria, transrrutted by night-feeding Anopheles mosquitoes, continue to infect military personnel deployed in locations throughout southwest Asia, sub-Saharan Africa, and the Korean pernnsula. A total of 425 cases of malaria were diagnosed in US military personnel between the years 2000 and 2005. 7 Most notable was the occurrence of 38 cases of vivax malaria in a 725man US Army Ranger task force that deployed to Afghanistan between June and September 2002. 4 Another significant malaria outbreak occurred during the deployment of 225 Marines to Liberia in which 80 Marines contracted falciparum malaria. 8 Since the early 1990s, US troops deployed in South Korea have consistently been at risk of exposure to vivax malaria. 9 Although there are sigillficant efforts underway from Depaltment of Defense (DoD) researchers, the Gates Foundation, and private industry to develop antimalarial drugs and malaria vaccines, a licensed vaccine is likely a decade or more away, and drug resistant parasites are continually appearing. IO In the interim, improved methods to reduce the risk of infection through mosquito control or personal protection are critical. Dengue Fever

We are currently witnessing a worldwide resurgence (and in some cases emergence) of arthropod-borne • Kenya-the US Army Medical Research Unit viral (arboviral) diseases, and dengue fever leads the Kenya (USAMRU-K) list as a public health threat. II The 4 dengue virus (DENY) strains are maintained in cycles involving • Indonesia - the US Naval Medical Research Urnt humans and the container-breeding Aedes aegypti NO.2 (NAMRU-2) mosquito, a vector that typically feeds on humans • Egypt-the US Naval Medical Research Unit during the daylight hours. The lack of treatment, the No.3 (NAMRU-3) explosive nature of this disease, and the potential for acquiring dengue hemorrhagic fever (a deadly form of • Peru-the US Naval Medical Research Center the disease) are causes for concern among DoD Detachment (NMRCD) planners. While DoD researchers are working towards This group of researchers is on the front lines working a vaccine that is protective against all 4 DENY to address the military's vector/pathogen surveillance serotypes, mosquito surveillance and control remain and control shortfalls. What follows is a summary of central to prevention and control of dengue fever the team's efforts associated with 5 priority arthropod- outbreaks.

July - September 2009

17

Operational Vector-borne Disease Surveillance and Control: Closing the Capabilities Gap through Research at Overseas Laboratories Chikungunya

1. Is there disease transmission in the area?

Chikungunya VUllS (CHIKV) IS an alphavirus transmitted to humans by container-breeding Aedes mosquitoes. The virus is endemic to Africa and various parts of Asia, including Indonesia and the Philippines. 12 This disease is currently showing a pattern of reemergence. In the last 5 years, explosive outbreaks have occurred in Kenya, the Seychelles, Comoros, Mayotte, Mauritius, Madagascar, India, and Italy.13 A specific example of the alarming attack rates occurred on the island of La Reunion where almost 40% of the island's total population of 785,000 fell ill in 2005-2006. 14 Recent outbreaks have also been reported in Singapore, Malaysia, and Thailand. Symptoms include fever, incapacitating joint pain, and rash which generally disappear after a few days. While CHIKV is rarely fatal, joint pain can persist for months or even years. Given the lack of a vaccine or treatment and the history of large epidemics, prevention of infection through vector control is paramount.

2. Which arthropod species are present and which

Leishmaniasis

ones are vectors of disease? 3. Which ones feed on humans? 4. Where does human-vector contact occur? 5. Where do the vector species breed and rest?

6. When and where should a vector control strategy be implemented? 7. What proportion of the vector population is susceptible or resistant to insecticides? 8. What vector control options will likely reduce

disease transmission? Malaria can be used as an example to highlight the importance of addressing the previous questions. Approximately 430 Anopheles species are found worldwide of which only 30 to 40 species transmit malaria in nature. I7 Of these, some feed indoors and others feed outdoors. If mosquito control programs are designed without determining when and where personnel are being exposed, they will likely fail to reduce the threat. However, with answers to the questions above, preventive medicine personnel may advise the use of insecticides inside sleeping areas to control a mosquito species which prefers to feed indoors at night. Although it is paramount that most, if not all, of the questions above be addressed prior to the implementation of a program, the current reality is that we do not yet have the capability to answer all of them. Seven of the major gaps are presented below, along with the measures that are being undertaken by military entomologists working overseas to overcome the recognized deficiencies.

Leishmaniasis presents itself in 2 mam forms: cutaneous leishmaniasis, which often results in skin lesions or attacks mucous membranes; and visceral leishmaniasis, which can lead to liver and other organ damage, and sometimes even death. Leishmaniasis is a parasitic infection caused by a variety of Leishmania species. Phlebotomine sand flies are involved in the transmission of Leishmania, from rodents and canids to humans. Sand flies are elusive, pinhead-sized insects of which little is understood about their biology and behavior. Consequently, control of these disease vectors continues to be a significant challenge for military entomologists. 15 No prophylactic drugs or vaccines are currently available, and emphasis is placed on preventive measures to break the cycle of DEFINING AND CLOSING THE CAPABILITIES transmission. 16 Task: Conduct Vector Surveillance

Gap: Adult mosquito and sand fly collection devices are minimally effective

DEFINING THE GAP

Effective vector-borne disease prevention relies on answering a core set of questions. Once these questions are answered, decision makers can design strategies based on evidence and tailored to the unique dynamics of their specific situation (in space and time). The fewer questions we can answer, and the more assumptions we make, the more likely we are to implement ineffective, one-size-fits-all solutions. At a minimum, the following questions must be answered. 16

18

GAPS

Problem. Numerous devices have been developed over the years to survey for Aedes (dengue/ chikungunya vectors) and Anopheles mosquitoes (malaria vectors).18 Sticky traps, visual traps, light traps and backpack aspirators are the most widely used tools for conducting mosquito surveillance,19-21 with Centers for Disease Control and Prevention (CDC) light traps (Figure 1) often considered the industry standard for mosquito surveillance. However, all of these trap types

http://www.cs.amedd.army.miljdasqaDocuments.aspx?type= 1

THE ARMY MEDICAL DEPARTMENT JOURNAL

for mosquitoes which feed during the day, such as DENV and CHIKV vectors.

> Not all night-feeding adult mosquitoes are attracted to the light source of a CDC trap. Mosquitoes only see in the visible light spectra of blue, green, and red. Incandescent light sources emit light most strongly in the infrared spectra and weakly in the visible light spectra of blue green 22 ' , and red. Therefore, even though Anopheles feed during the night, potentially important vectors are often "repelled" by the light source.

> The trap should be augmented with a carbon

Figure 1. A CDC light trap.

have drawbacks. 18 For example: sticky traps can damage sampled mosquitoes, the degree of success with backpack aspirators is higWy dependent on the collector/inspector, visual traps are generally of lower efficiency, and CDC light traps lack an olfactory-based attractant and contain a light source that has the unintended effect of repelling some mosquito species. Ideally, human landing counts (HLCs) can be used to evaluate the efficacy of vector control. This technique involves collecting host-seeking arthropod females that land on an individual human's exposed legs. Data collected using this technique generally correlates well with local vector population densities. The HLCs can also be used to help determine entomological inoculation rates, which are true estimates of the disease risk posed to humans. While surveillance using ffi.,Cs is the most effective approach for determining mosquito densities, the ethical issue of placing humans at risk for contracting disease from pathogens originating from mosquito vectors makes this approach less appealing in today's environment. Currently, PM assets depend on the CDC light trap (or a related version) to conduct most adult mosquito surveillance. The main attractant is a 4- to 6-watt incandescent light bulb. As the mosquito approaches the light source, it is drawn downward into a collection bag by a fan mounted just below the light bulb. This surveillance tool has significant limitations with regard to collecting diseas~ vectors: ~

dioxide source to enhance trap effectiveness. The carbon dioxide source might come in the form of dry ice, granular CO 2-sachets, or a canister of CO2 , Blood-feeding mosquitoes use a combination of olfactory cues in addition to visual cues to find a suitable host. Carbon dioxide is considered to be a principal olfactory attractant.

> The efficiency of converting electrical current to light using incandescent light bulbs is exceptionally low (approximately 6%). The remainder (94%) is often dispersed as heat or infrared radiation. 22 As a consequence, this device consumes a great deal of energy.

> The effectiveness of these traps for collecting sand flies has not been systematically evaluated.

Solutions BG-Sentinel Trap (BGS) (Biogents AG, Regensburg,

Germany). The BGS (Figure 2) has shown significant promise as a tool for collecting Ae aegypti,23-26 and Ae albopictus. 27 To our knowledge, this device has not been evaluated for malaria vectors in Asia. The BGS uses a blend of mosquito attractants consisting of lactic acid, ammonia, and caproic acid, substances all found on human skin. The blend is released in a fixed ratio from a dispenser known as the BG Lure?3 The efficacy of the BGS (with and without carbon dioxide) relative to other surveillance devices for collecting DENV and malaria vectors is being evaluated in Thailand.

Bed Net Traps. An alternative to HLCs is needed, particularly in areas of high disease transmission. The performance of a self-supporting bed net trap is The trap is only effective for some mosquito undergoing evaluation by Navy entomologists at species that feed at night (ie, Anopheles). The NAMRU-2. Preliminary results show that a CDC light trap is an inadequate surveillance tool lightweight (2 kg), easy-to-assemble bed net trap July - September 2009

19

Operational Vector-borne Disease Surveillance and Control: Closing the Capabilities Gap through Research at Overseas Laboratories studies are being conducted to determine the efficacy of a wide range of semiochemicals, either repellents or attractants, on the activity of sand fli~s. Pheromones from Lutzomyia longipalpis (leishmaniasis vector) males have shown significant promise. 35 Like many sand flies, L longipalpis is a lekking species, one in which males gather for the purposes of a competitive mating display. Females are attracted to displays of male wing-fanning behavior and pheromones released by the male. It is therefore likely that traps baited with male pheromones will attract female sand flies in the field (their potential has already been shown in the laboratory). Efforts are underway in Colombia where scientists from the NMRCD, in collaboration with Rothamsted Research (Harpenden, Hertfordshire, UK)20 are evaluating the efficacy of these pheromones as baits in a variety of commercial traps placed in jungle encampments in the Colombian Amazon. collected significantly greater numbers of Anopheles n"'f'f'f'nt"!' spp and Culex spp (vectors of Japanese encephalitis "'t1"~",)~ virus and filariasis) than a CDC trap. The trap, shown in Figure 3, is designed to protect the person (the '~~~~~~\~JJ~ attractant) in the bed net while simultaneously trapping ~ (in an outer tent structure) vectors that can be identified and tested for human pathogens. In areas where disease transmission is very high or drug resistant pathogens occur, collections of mosquitoes could be made while minimizing the risk to the collector. 28•29 Mass Trapping Techniques for Surveillance/Control. Traps that generate CO 2 by catalyzing propane have demonstrated a reduction in nuisance mosquito or 3o 33 biting midge populations. . Little is known regarding the effectiveness of these traps on reducing disease vector species in isolated, tropical environ33 Manufacturers of commercially available ments. traps claim the ability to control mosquito populations over an area as large as one acre.* Future evaluations of this technology at overseas field sites will determine the efficacy of a commercial mosquito trap in reducing prevalence of mosquito populations in a specific area. Sand Fly Attractants. Modified CDC light traps were recently tested in southern Egypt by NAMRU-3 researchers. The light traps were modified to accommodate light emitting diodes, and proved to be very effective for sand fly surveillance.34 At present, field *Example: Mosquito Magnet®, Woodstream Corp, Lititz, PA Information available at http://www.mosquitomagnet.com 20

l...-Fi-=.g_ur_e_3_._T_h_e_b_e_d_n_et_tr_a;....p. _ Task: Identify Vector Species Gap: Limited availability of country-specific taxonomic keys and limited knowledge of species' bionomics, relative vector status, and distribution Problem. The Walter Reed Biosystematics Unit has made significant strides in designing user-friendly, regional keys for the identification of mosquitoes and sand flies worldwide. These keys have proven their utility, most especially in southwest Asia. However, regionally relevant identification keys along with descriptions related to the feeding, breeding, and resting behavior, relative vector status, and distribution of species are still lacking for much of the tropics. Without these references, PM planners are not able to answer the relevant questions which drive implementation of sound control programs.

http://www.cs.amedd.army.mil/dasqaDocuments.aspx?type:::1


environmental and human health risks often associated with insecticide application. For example, the malaria Sand Fly Biology and Taxonomic Research. The dipstick assay is a rapid, one-step procedure that uses a NAMRU-3 has been conducting extensive sand fly test strip capable of detecting and then differentiating research and surveillance in countries throughout between infections of P falciparum and P vivax in Africa and the Middle East for over 50 years. During adult mosquito collections within minutes. 48 This that time, the NAMRU-3 Vector Biology Research particular hand-held device is of lower cost and is very Program (VBRP) has determined the vector status of user-friendly relative to polymerase chain reaction numerous Phlebotomus species found throughout the methods, and can potentially identify areas where the Middle East and African region,36-38 and has developed risk of contracting malaria is high. Such a tool can a better understanding of sand fly ecology in various help to prioritize control efforts and has significant countries within the aforementioned region, including impact when requesting support or the assistance of extensive bionomics studies of sand flies in the the command. This type of rapid screening tool is not Sinai 36,39 and in southern Egypt, where sand fly available for most vector-borne pathogens. daytime resting sites were recently discovered for the fIrst time. 4o Sand fly species distributions have been Solutions. The overseas laboratories are actively determined in Djibouti,41 and NAMRU-3 is involved in the field evaluation of hand-held dipstick completing compilations for Egypt and parts of Ghana. assays for the detection of leishmaniasis, DENY, Further, wide-scale species distribution projects are Japanese encephalitis virus, and Rift Valley fever currently underway in Afghanistan and Libya. virus. In addition, in collaboration with both the US Collectively, NAMRU-3 has produced taxonomic keys Army Research Institute for Infectious Diseases and for the sand flies of Afghanistan, Egypt, Ghana, Sudan the US Air Force 59th Clinical Research Division, (B.D.F., unpublished data, 2009), and Djibouti. 41 To entomologists at AFRIMS, NAMRU-3, and USAMRU supplement the morphological identifIcation of sand -K are conducting field evaluations of real-time flies, VBRP has a rapidly expanding polymerase chain polymerase chain reaction assays to detect vectorreaction component which allows for the molecular borne pathogens. Many of these assays are designed for the Joint Biological Agent Identification and DiagidentifIcation of sand flies. nostic System using the Ruggedized Advanced PathoMosquito Keys. World-reno,¥ned mosquito taxonomist gen Identification Device (Idaho Technology IncorDr Rampa Rattanarithikul has spent decades at porated, Salt Lake City, Utah) as the platform. 49 ,5o AFRIMS dissecting, classifying, and analyzing mosquitoes. 42 With the assistance of illustrator Task: Provide Personal Protective Measures Prachong Panthusiri, they are on the verge of Gap: The military has yet to field bed nets, tents, or other materials which have been treated with completing the last volume of a 6-volume publication long lasting insecticides entitled Illustrated Keys to the Mosquitoes of Thailand. 4J -47 This tool will be exceptionally valuable Problem. The use of insecticide-treated nets (ITNs) for preventive medicine assets deploying to southeast and insecticide-treated tents is regarded as one of the Asia, especially for those associated with the annual most promising measures available to reduce vectorCobra Gold exercises in Thailand and current borne disease transmission. 51 However, treatment of operations in the Republic of the Philippines. ITNs with insecticide is performed in the field (not at the factory) which presents an added burden for PM Task: Conduct Pathogen Surveillance assets. Application of insecticide to bed nets and tents Gap: Rapid pathogen surveillance devices are is labor-intensive and not often a command priority. lacking Problem. While a disease vector may be present in a Solutions Solutions

particular area, the broad application of control measures may not necessarily be warranted. Pathogen surveillance tools allow for the effective local targeting of control measures, thereby enhancing the possibility of managing the disease, while reaping the benefits of reduced costs and avoidance of the potential

Long-lasting Insecticidal Net (LLIN) Evaluations. Manufacturers have developed LLINs such as Perma-Net® (Vestergaard Frandsen, Lausanne, Switzerland) which are ready-to-use, factory pretreated nets. Many of these nets are designed to release insecticide slowly so that the nets retain their efficacy after repeated


21

Operational Vector-borne Disease Surveillance and Control: Closing the Capabilities Gap through Research at Overseas Laboratories

washings. Some LLINs are said to require no further treatment during their physical lifespan of 4 to 5 years. 51 Currently, AFRIMS is evaluating the longterm efficacy of LLINs on vector densities in villages located in western Thailand. If shown to be effective, LLINs may be a valuable alternative to the fieldapplication of insecticide to bed nets.

daunting and is minimally effective if surrounding areas are left untreated, or if coverage in the target area is low. What is lacking is an expedient, low risk, efficient, and sustainable approach to achieving epidemiologically-relevant levels of Ae aegypti population suppression.

Solutions Insecticide-impregnated Tent Evaluations. US Anny Deployable Rapid Assembly Shelter (DRASH) tents are woven from a noncanvas XYTEX® (DHS Technologies LLC, Orangeburg, New York) fabric, which is polyester-coated with polyvinyl chloride. Studies are underway in southeastern Thailand to determine whether insecticide-impregnated tents are indeed a viable approach for protecting Soldiers from vector-borne disease over the long-term. If this is found to be the case, further studies will then evaluate the utility of insecticide-impregnated DRASH tents (assuming that the technology is developed) in affording protection for Soldiers. Task: Conduct Vector Control Gap: Lack of effective and sustainable control methods for Aedes mosquitoes (CHIKV and DENV vectors)

Problem. Given adequate personnel, community involvement, money, and time, Ae aegypti population control can be achieved through sanitation and the elimination of mosquito breeding sites. This option is often not viable for military pest controllers during deployments. Effective source reduction is difficult when the military has no control of areas surrounding encampments occupied by US personnel. Chemical control using DoD-registered larvicides (larval stage insecticides) such as methoprene, temephos, and Bacillus thuringiensis israelensis (Bti) and various adulticides (adult stage insecticides) has proven effective in managing both larval and adult populations respectively of Ae aegypti. 52 However, these options have obvious limitations when it comes to deployments and protecting the Warfighter. Indoor adulticide application can effectively reduce Ae aegypti populations but must be applied inside occupied structures on a regular basis. This can be difficult to justify as a preventive measure and is often unachievable. In general, the military is more likely to practice indoor adulticide application in response to disease transmission rather than as a preventive measure. Traditional larval control is logistically

22

Resting/oviposition Lures Treated with Pyriproxyfen. Pyriproxyfen is classified as an insect growth regulator and a potent inhibitor of embryogenesis, metamorphosis, and adult formation in insects. 53 In addition, it has been shown to decrease the fertility and fecundity of Ae aegypti adults that develop from sublethally exposed larvae.54 Evidence also suggests that adult mosquitoes not killed by contact with pyriproxyfen that is applied to breeding containers can actually carry the chemical to uncontaminated environments. The tiny doses of pyriproxyfen that are moved can then negatively affect the development of susceptible larvae.55 Pyriproxyfen has long residual efficacy yet has an .excellent mammalian toxicity profile. The most promising scenario involves females resting on surfaces treated with pyriproxyfen, picking up tiny doses of chemical that sterilize the females which then transports the pesticide to other breeding sites. Work conducted by the NMRCD, Rothamsted Research, and the Peruvian health authorities suggests that this approach has considerable potential. The NMRCD is designing a variety of simple resting and oviposition lures which will attract Ae aegypti and which can be treated with pyriproxyfen. The efficacies of these treated lures on fecundity and on the horizontal transfer of pyriproxyfen will be evaluated under seminatural conditions with future plans for field evaluations to establish the optimal distribution of such treated lures. Pyriproxyfen-treated Ovitrap/resting Station Device Design/evaluation. Researchers at AFRIMS are desiglling and evaluating a visually attractive, pyriproxyfen-treated ovitrap (egg trap)/resting station device. It is clear that Ae aegypti females tend to spread their eggs among many sites. This behavior should improve the natural transfer of pyriproxyfen. Ae aegypti tend to remain relatively close to their larval habitat, with maximum dispersal distances around 100 to 200 m,56 therefore significant control (or local eradication) via this approach is within reason. This is particularly relevant in the context of a rllilitary

http://www.cs.amedd.army.miljdasqaDocuments.aspx?type= 1


camp where sanitation is high and larval habitat can be minimized. Initial lab evaluation of prototypes is underway using field cages/tunnels. Field trials are scheduled to assess the impact of the final product, spatially arranged as a barrier-like treatment, on Ae aegypti densities in a simulated military camp within a dengue-endemic village. ProVector™ Trap Evaluations. A possible tool for the control of adult Ae aegypti populations currently being evaluated at USAMRU-K is the ProVector™ trap (MIT Holding Inc, Savannah, Georgia). This low cost trap mimics visual and chemical cues used by mosquitoes in search of a sugar meal. The trap is designed in such a way that only mosquitoes can feed on it, thus reducing the possibility of exposure to nontarget organisms and accidental environmental contamination. These traps, designed at the Biodefense and Infectious Disease Laboratory at Georgia Southern University, use a formulation of Bacillus thuringiensis israeliensis bioinsecticide as the active ingredient. This trap will be evaluated not only for its efficacy as a method for DENY and malaria vector control tool, but also as a tool for increasing the efficacy of Ae aegypti surveillance. Push-pull System. Research is underway at NMRCD to develop a novel insecticide treated material (ITM) push-pull system to reduce Ae aegypti inside homes where they are most likely to feed on humans and transmit DENY. The system is comprised of ITMs designed to repel Ae aegypti from inside homes and an attractive, lethal trap positioned outside the home to pull the mosquitoes from the peridomestic environment. Following proof-of-concept, long-term goals include defining the public health impact of the system through epidemiological studies for operational refmement.

efficacy. Effective vector control operations thus require more frequent spraying with obvious repercussions on sustainability. A DDT alternative with similar durability and effectiveness is desperately needed. Solution. Pyrethroids have replaced many older insecticides because of their effectiveness and relative safety for the applicator. 58 The chemical structure of pyrethroids resembles a component of the natural botanical insecticide known as pyrethrum. Pyrethroids are highly toxic to most insects at very low rates of application. While pyrethroids do not measure up to DDT in terms of stability, there is evidence that the pyrethroid bifenthrin may be efficacious against mosquitoes for a considerable length of time postapplication (6 weeks) when applied to vegetation relative to other insecticides. 59 TalStarOne™ (FMC Corp, Philadelphia, Pennsylvania) (bifenthrin 7.9%) is EPA-registered and endorsed by the Armed Forces Pest Management Board for use on military installations and during deployments. Recent work at USAMRU-K, in partnership with the US Department of Agriculture Center for Medical and Veterinary Entomology, have shown that bifenthrin-treated camouflage nets provide an effective protective barrier against mosquitoes and sand flies, significantly reducing total trap numbers for over 6 weeks. Additionally, mortality rates were significantly higher for those vectors that made it through the nets, suggesting that treated nets provide protection beyond the initial barrier effect for which they were tested. Evaluations are also being performed in Thailand to determine the extent to which this insecticide is effective for the long-term control of malaria vectors when applied to vegetation along the perimeter of a village (Figure 4). Gap: No effective sand fly control strategies

Gap: No effective replacement for the insecticide

Problem. Unlike mosquito control, sand flies pose numerous problems that prevent the coherent Problem. The successful eradication of malaria from development of an effective control strategy. Sand fly the developed world and large portions of tropical Asia breeding habitats are much more cryptic and often and Latin America was due largely to the widespread impossible to identify, thus preventing the use of DDT. 57 The effectiveness of DDT is primarily a development of any effective larviciding strategy. result of its long lasting persistence. Ironically, this Sand fly populations are extremely focal, with quality also led to the cancellation of its registration by significant geographical and seasonal variations. Sand the Environmental Protection Agency. 58 Modern fly surveillance is a challenge and without the alternatives to DDT are relatively unstable in the surveillance data, it is difficult to make sound environment and therefore have shorter windows of decisions for targeted sand fly control operations. In

DDT


23


the absence of better alternatives, deployed personnel currently revert to mosquito control methods. Sustainable and evidence-based strategies for targeting sand flies are clearly needed. Solution. Rodent Pass-through System. The effectiveness of a rodent pass-through system to control sand fly populations is being evaluated at USAMRU-K. Laboratory studies have shown that diflubenzuron can prevent synthesis of chitin (the material composing the outer skeleton of arthropods). Diflubenzuron is nontoxic to rodents and remains active after passage through the rodent digestive tract. 60 Since the larvae of many sand fly species feed on rodent feces,61 this may provide the first truly effective technique for targeting larval sand flies. Once baits are formulated for the targeted rodent fauna, diflubenzuron will be incorporated and the baits offered on a monthly basis. It is important to note that this would target native rodent populations in areas where troops are deployed, not pest rodent populations that are normally targeted with anticoagulant baits. Also, preliminary work is underway to evaluate the efficacy of using a sugar solution spray as bait for targeting adult male and female sand flies in search of sugar meals.

CONCLUSION

There is a well recognized gap between the resources required and those available to manage the risks to the Warfighter posed by malaria, dengue fever, chikungunya virus, leishmaniasis, and myriad other vector-borne disease threats. Vector control experts are expected to accurately evaluate the vector-borne disease threat and then make sound decisions to reduce that threat. Following the models of the pioneering work of Reed, Gorgas, and others, US Army, Navy, and Air Force researchers working overseas are helping to close this gap. Their efforts are enhancing the combatant commander's ability to identify and mitigate the threat posed by these vector-borne diseases. REFERENCES

1. Shultz HA. Department of Defense doctrine and materiel for protecting personnel from biting arthropods. J Trav Med. 2001;8(3): 133-138. 2. Petri WA. Presidential address, America in the world: 100 years of tropical medicine and hygiene. Am J Trop Med Hyg. 2004;71(1):2-16. 3. Holway RT. Contributions of insecticides to national defense. Bull Entomol Soc Am. 1962;8(2):76-80. 4. Kotwal RS, Wenzel RB, Sterling RA, Porter WD, Jordan NN, Petruccelli BP. An outbreak of malaria in US Army Rangers returning from Afghanistan. J Am Med Assoc. 2005;293(2):212-216. 5. Burnette WN, Hoke CH, Scovill J, et al. Infectious diseases investment decision evaluation algorithm: a quantitative algorithm for prioritization of naturally occurring infectious disease threats to the US military. Mil Med. 2008;173(2):174-181. 6. Porter WD. Imported malaria and conflict: 50 years of experience in the US military. Mil Med. 2006;171 (10):925-928. 7. Ciminera P, Brundage J. Malaria in US military forces: a description of deployment exposures from 2003 through 2005. Am J Trop Med Hyg. 2007;76 (2):275-279. 8. Debboun M, Robert L, O'Brien L, Johnson R, Berte S. Vector control and pest management. Army Med Dept J. April-June 2006:31-39.

Figure 4. Application of pyrethroid bifenthrin on the perimeter of jungle village in Thailand in a test of longterm effectiveness.

24

9. Park JW, Klein TA, Lee HC, et al. Vivax malaria: a continuing health threat to the Republic of Korea. Am J Trop Med Hyg. 2003;69(2): 159-167.

http://www.cs.amedd.army.mil/dasqaDocuments.aspx?type= 1


10. Fuller T. Ominous signs in malaria fight: resistance to best hope against disease is found in Cambodia. International Herald Tribune. January 26, 2009:1, 4.

22. Cohnstaedt LW, Gillen n, Munstermann LE. Lightemitting diode technology improves insect trapping. J Am Mosq Control Assoc. 2008;24(2):331-334.

11. Gubler DJ. The global emergence/resurgence of arboviral diseases as public health problems. Arch Med Res. 2002;33(4):330-342.

23. Krockel U, Rose A, Eiras AE, Geier M. New tools for surveillance of adult yellow fever mosquitoes: comparison of trap catches with human landing rates in an urban environment. J Am Mosq Control Assoc. 2006;22(2):229-238.

12. Halstead SB, Scanlon JE, Umpaivit P, Udomsakdi S. Dengue and chikungunya virus infection in man in Thailand, 1962-1964. IV. Epidemiologic studies in the Bangkok metropolitan area. Am J Trop Med Hyg. 1969;18(6):997-1021. 13. Pialoux G, Gauzere BA, Jaureguiberry S, Strobel M. Chikungunya, an epidemic arbovirosis. Lancet Infect Dis. 2007;7(5):319-327. 14. Enserink M. Infectious diseases. massive outbreak draws fresh attention to little-known virus. Science. 2006;311(5764):1085. 15. Coleman RE, Burkett DA, Putnam JL, et al. Impact of phlebotomine sand flies on US military operations at Tallil Air Base, Iraq: 1. background, military situation, and development of a "leishmaniasis control program". J Med Entomol. 2006;43(4):647662. 16. Malaria Entomology and Vector Control, Learner's Guide. Geneva: World Health Organization; July 2003. Publication WHO/CDS/CPE/SMT/2oo2.18 Rev 1 Part I. Available at: http://apps.who.int/malaria/ docs/evc_Ig2oo3.pdf. Accessed July 2,2009. 17. Anopheles Mosquitoes home page. Centers for Disease Control and Prevention website. Available at: http://www .cdc.gov/malaria/biology /mosqui to/. Accessed July 21,2009.

18. Service MW. Community participation in vectorborne disease control. Ann Trop Med Parasitol. 1993;87(3):223-234. 19. Clark GG, Seda H, Gubler OJ. Use of the "CDC backpack aspirator" for surveillance of Aedes aegypti in San Juan, Puerto Rico. JAm Mosq Control Assoc. 1994;10(1):119-124. 20. Jensen T, Willis OR, Fukuda T, Barnard DR. Comparison of bidirectional Fay, omnidirectional, CDC, and duplex cone traps for sampling adult Aedes albopictus and Aedes aegypti in north Florida. J Am Mosq Control Assoc. 1994;10(1):74-78. 21. Ordonez-Gonzalez JG, Mercado-Hernandez R, FloresSuarez AE, Fernandez-Salas I. The use of sticky ovitraps to estimate dispersal of Aedes aegypti in northeastern Mexico. J Am Mosq Control Assoc. 2001 ;17(2):93-97.

24. Maciel de Feitas R, Eiras A, Lourenco de Oliveira R. Field evaluation of effectiveness of the BG sentinel, a new trap for capturing adult Aedes aegypti (Diptera: Culicidae). Mem Inst Oswaldo Cruz. 2006;101:321325. 25. Williams CR, Long SA, Russell RC, Ritchie SA. Field efficacy of the BG-Sentinel compared with CDC backpack aspirators and C02-baited EVS traps for collection of adult Aedes aegypti in Cairns, Queensland, Australia. J Am Mosq Control Assoc. 2006;22(2):296-300. 26. Williams CR, Long SA, Webb CE, et al. Aedes aegypti population sampling using BG-Sentinel traps in north Queensland Australia: statistical considerations for trap deployment and sampling strategy. J Med Entomol. 2007;44(2):345-350. 27. Meeraus WH, Armistead JS, Arias JR. Field comparison of novel and gold standard traps for collecting Aedes albopictus in northern Virginia. J Am Mosq Control Assoc. 2008;24(2):244-248. 28. Trape JF. The public health impact of chloroquine resistance in Africa. Am J Trop Med Hyg. 2001;64 (suppl):12-17. 29. Aslam NA. A modified design of a bed-trap for sampling malaria vectors [World Health Organization online library]. June 30, 1966. Available at: http:// whqlibdoc. who.int/malariaiWHO_Mal_66.555.pdf. Accessed July 2, 2009. 30. Cilek JE, Halloman CF. The effectiveness Mosquito Magnet trap for reducing biting (Diptera: Ceratopogonidae) populations in residential backyards. J Am Mosq Control 2005;21(2):218-221.

of the midge coastal Assoc.

31. Cilek JE, Kline DL, Hallmon CF. Evaluation of a novel removal trap system to reduce biting midge (Diptera: Ceratopogonidae) populations in Florida backyards. J Vector Ecol. 2003;28(1):23-30. 32. Henderson JP, Westwood R, Galloway T. An assessment of the effectiveness of the Mosquito Magnet Pro model for suppression of nuisance mosquitoes. J Am Mosq Control Assoc. 2006;22 (3):401-407.


25


33. Kline DL. Traps and trapping techniques for adult mosquito control. JAm Mosq Control Assoc. 2006;22 ·(3):490-496. 34. Hoel DF, Butler JF, Fawaz EY, Watany N, EIHossary SS, Villinski J. Response of phlebotomine sand flies to light-emitting diode-modified light traps in southern Egypt. J Vector Ecol. 2007;32(2):302308. 35. Hamilton JG. Sandfly pheromones. Their biology and potential for use in control programs. Parasite. 2008;15(3):252-256. 36. Hanafi HA, el-SawafBM, Beavers GM. The effect of Leishmania major on some biological parameters of Phlebotomus papatasi (Diptera: Psychodidae) from endemic and nonendemic areas in Egypt. J Egypt Soc Parasitol. 1999;29(2):293-305.

44. Rattanarithikul R, Harbach RE' Harrison BA, Panthusiri P, Jones JW, Coleman RE. Illustrated keys to the mosquitoes of Thailand. II. Genera Culex and Lutzia. Southeast Asian J Trop Med Publ Health. 2005;36(suppI2):1-97. 45. Rattanarithikul R, Harrison BA, Harbach RE' Panthusiri P, Coleman RE. Illustrated keys to the mosquitoes of Thailand. IV. Anopheles. Southeast Asian J Trop Med Publ Health. 2006;37(suppl 2):1128. 46. Rattanarithikul R, Harrison BA, Panthusiri P, Coleman RE' Illustrated keys to the mosquitoes of Thailand I. Background; geographic distribution; lists of genera, subgenera, and species; and a key to the genera. Southeast Asian J Trop Med Publ Health. 2005;36(suppll):1-80.

37. Hanafi HA, Fryauff DJ, Dykstra EA, Szumlas DE. Laboratory demonstration of the acquisition and development of Leishmania major in the sand fly Phlebotomus kazeruni (Diptera: Psychodidae). J Egypt Soc Parasito!' 2007;37(1):227-241.

47. Rattanarithikul R, Harrison BA, Panthusiri P, Peyton EL, Coleman RE. Illustrated keys to the mosquitoes of Thailand m. Genera Aedeomyia, Ficalbia, Mimomyia, Hodgesia, Coquillettidia, Mansonia, and Uranotaenia. Southeast Asian J Trop Med Publ Health. 2006;37(suppll): 1-85.

38. Hanafi HA, Beavers GM, Dykstra EA. New record of Phlebotomus sergenti, the vector of Leishmania tropica, in the southern Nile valley of Egypt. J Am Mosq Control Assoc. 2001;17(4):272-274.

48. Ryan JR, Dave K,- Collins KM, et al. Extensive multiple test centre evaluation of the VecTest malaria antigen panel assay. Med Vet Entomol. 2002;16 (3):321-327.

39. Hanafi HA, Fryauff DJ, Modi GB, Ibrahim MO, Main AI. Bionomics of phlebotomine sandflies at a peacekeeping duty site in the north of Sinai, Egypt. Acta Trop. 2007;101(2):106-114.

49. McAvin JC, Escamilla EM, Blow JA, et al. Rapid identification of dengue virus by reverse transcription -polymerase chain reaction using field deployable instrumentation. Mil Med. 2005;170(12): 1053-1 059.

40. Hogsette JA, Hanafi HA, Bernier UR, et al. Discovery of diurnal resting sites of phlebotomine sand flies in a village in southern Egypt. J Am Mosq Control Assoc. 2008;24(4):601-603.

50. McAvin JC, Powers MD, Blow JA, Putnam JL, Huff WB, Swaby JA. Deployable, field sustainable, reverse transcription-polymerase chain reaction assays for rapid screening and serotype indentification of dengue virus in mosquitoes. Mil Med. 2007;172(3):329-334.

41. FryauffDJ, Cope SE, Presley SM, et al. Sand flies of the Republic of Djibouti: ecological distribution, seasonal population trends, and identification of species. J Vector Ecol. 1995;20(2):168-188. 42. Pinkowski J. Scientist at work, Rampa Rattanarithikul: pesky critter makes for a busy career. New York Times. 22 July 2008, Technology section. Available at: http://www.nytimes.com/2008/07/22/ science/22prof.htrnl?scp=1&sq=&st=nyt. Accessed July 2, 2009. 43. Rattanarithikul R, Harbach RE, Harrison BA, Panthusiri P, Coleman RE. Illustrated keys to the mosquitoes of Thailand V. Genera Orthopodomyia, Kimia, Malaya, Topomyia, Tripteroides, and Toxorhynchites. Southeast Asian J Trop Med Publ Health.2007;38(suppI2):1-65.

26

51. Msangi S, Lyatuu E, Masenga C, Kihumo E. The effects of washing and duration of use of long-lasting insecticidal nets (perrnaNets) on insecticidal effectiveness. Acta Trop. 2008;107(1):43-47. 52. Gubler DJ. The changing epidemiology of yellow fever and dengue, 1900 to 2003: full circle? Comp Immunol Microbiol Infect Dis. 2004;27(5):319-330. 53. Ishaaya I, Horowitz AR. In focus: IPM using novel insecticides and other approaches. Pest Manag Sci. 2007;63(8):729. 54. Dash AP, Ranjit MR. Comparative efficacy of aphid extracts and some juvenoids against the development of mosquitoes. J Am Mosq Control Assoc. 1992;8 (3):247-251.

http://www.cs.amedd.army.mil/dasqaDocuments.aspx?type=l


55. Hoh T, Kawada H, Abe A, Eshita Y, Rongsriyam Y, Igarashi A. Utilization of bloodfed females of Aedes aegypti as a vehicle for the transfer of the insect growth regulator pyriproxyfen to larval habitats. JAm Mosq Control Assoc. 1994;10(3):344-347. 56. Harrington LC, Scott TW, Lerdthusnee K, et al. Dispersal of the dengue vector Aedes aegypti within and between rural communities. Am J Trop Med Hyg. 2005 ;72(2):209-220. 57. Trigg PI, Kondrachine AV. Commentary: malaria control in the 199Os. Bull World Health Org. 1998;76 (1):11-16. 58. Pedigo LP, Rice ME. Entomology and Pest Management. 5th ed. Upper Saddle River, New Jersey: Prentice Hall, Inc; 2006. 59. Royal A. A new tool for the control of mosquitoes, biting midges, and flies. Wing Beats. 2004;151:18-19, 22. 60. Mascari TM, Mitchell MA, Rowton ED, Foil LD. Evaluation of novaluron as a feed-through insecticide for control of immature sand flies (Diptera: Psychodidae). J Med Entomol. 2007;44(4):714-717.

AUTHORS

MAJ Evans is Deputy Chief, Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. CPT Clark is Chief, Department of Entomology & Vector Borne Diseases, US Army Medical Research Unit-Kenya. LT Barbara is Head, Medical Entomology Department, US Naval Medical Research Unit No.2, Jakarta, Indonesia. LT Mundal is Director, Entomology Research Program, US Naval Medical Research Center Detachment, Lima Peru. LT Furman is Head, Vector Biology Research Program, US Naval Medical Research No.3, Cairo, Egypt. James McAvin is a visiting scientist at the Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand. MAJ Richardson is Chief, Department of Entomology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand.

61. Neronov VM, Gunin PD. Structure of natural foci of zoonotic cutaneous leishmaniasis and its relationship to regional morphology. Bull World Health Organ. 1971;44:577-584.

Sand Fly

Asian Tiger MosqUito


27